Download Cough, fever and weight loss in a young male

Copyright #ERS Journals Ltd 2002
European Respiratory Journal
ISSN 0903-1936
Eur Respir J 2002; 19: 1210–1213
DOI: 10.1183/09031936.02.00283802
Printed in UK – all rights reserved
CASE FOR DIAGNOSIS
Cough, fever and weight loss in a young male
R. Summer*, J. Zacks#, M. Ieong*, A. O9Regan*
Case history
A 48-yr-old male was admitted with 6 months of
nonproductive cough, fever, and weight loss. These
symptoms progressed despite a course of antibiotics
prescribed for presumed community-acquired pneumonia 2 months prior to admission. A chest radiograph
taken at that time is shown in figure 1a. The patient
denied any other symptoms, including skin rash,
a)
b)
Fig. 1. – a) Normal chest radiograph 2 months prior to admission.
b) Admission chest radiograph. Large nodules are seen in both lungs.
joint pain, and extremity numbness and weakness.
Past medical history was significant for infection
with Hepatitis-C virus and an accidental shotgun
wound. The patient had a 30-pack-yr smoking history,
remote use of injected heroin and cocaine and distant
ethanol abuse. There was no occupational exposure
to asbestos or silica, no recent travel and he had no
pets or hobbies. He was not taking any medications.
On physical examination the patient was diaphoretic with a temperature of 39.4u C, pulse 107
beat?min-1, blood pressure 133/75 mmHg, respiration
28 breaths?min-1 and oxygen saturation of 88% on
room air. Chest examination revealed bilateral basilar
crackles. A 2-cm lymph node that was firm, mobile
and not tender was palpated in the right axilla. The
rest of the examination was normal.
Laboratory studies demonstrated a white blood
count of 2.46109 L-1 (53% lymphocytes, 25% neutrophils, 15% monocytes, 3% eosinophils and 2% bands),
haematocrit of 30% and platelet count 77610 10 L-1.
Serum chemistries, renal and liver function tests were
normal. Lactate dehydrogenase was normal. The
patient was human immunodeficiency virus (HIV)
negative. Chest radiography (fig. 1b) was performed
on admission, followed by computed tomography
(CT) scan of the chest (fig. 2). Over the course of the
next week repeat blood, urine, and sputum cultures
were sterile and a bone marrow aspirate and biopsy
was nondiagnostic. A biopsy of the right axillary
lymph node was performed (fig. 3).
Fig. 2. – Chest computed tomography scan.
*The Pulmonary Centre and and #The Dept of Pathology, Boston University School of Medicine, Boston, MA, USA.
Correspondence: A. O9Regan, Assistant Professor of Medicine, The Pulmonary Center, Boston University School of Medicine, 715 Albany
Street, Boston, MA 02118, USA.
Fax: 1 6175368093. E-mail: [email protected]
COUGH, FEVER AND WEIGHT LOSS IN A YOUNG MALE
a)
b)
c)
d)
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Fig. 3. – a) The dissected lymph node stained with haemotoxylin and eosin. b) The same section under higher magnification. Atypical
lymphocytes are highlighted by solid arrows. c) B-lymphocytes are stained with CD20 marker (brown cells are indicated by an open
arrow). Abundant T-lymphocyte population (solid arrow) surrounds the CD20 positive cells. d) Positive staining for small Ebstein-Barr
encoded ribonucleic acid particles. Scale bars=50 mm.
BEFORE TURNING THE PAGE, INTERPRET THE CHEST RADIOGRAPHS (FIGS. 1a
AND b), THE COMPUTED TOMOGRAPHY SCAN (FIG. 2) AND THE PHOTOMICROGRAPH (FIG. 3), AND SUGGEST A DIAGNOSIS.
1212
R. SUMMER ET AL.
Interpretations
Chest radiographs
The frontal chest radiograph (fig. 1a) taken
2 months prior to admission is normal. The small
circular radio-opaque nodules in the chest represent
metallic pellets from a prior shotgun accident.
The repeat film on admission (fig. 1b) demonstrates
large nodules of variable size predominantly involving
the lower lung fields.
Computed tomography
The chest CT scan (fig. 2) shows multiple nodular
masses throughout the lungs. Nodules were not
calcified and there was no cavitation. There was no
mediastinal adenopathy or pleural disease.
Pathology
Figure 3a shows the dissected lymph node (magnification610), demonstrating a nodular perivascular
infiltrate with extensive tissue necrosis consistent with
angiitis and granulomatosis. No epithelioid cells or
granulomas are seen.
In figure 3b, higher magnification of the perivascular infiltrate confirms the presence of polymorphic
lymphocytic cells with occasional large atypical
mononuclear cells.
Figure 3c demonstrates, by immunohistochemistry,
that the large atypical cells express B-cell (CD20)
antigens. Deoxyribonucleic acid extracted from the
tissue and amplified using the polymerase chain
reaction demonstrated a rearrangement of the immunoglobulin heavy chain, consistent with a monoclonal
B-cell population (not shown).
As shown in figure 3d, the large cells also
demonstrate nuclear staining for small Ebstein-Barr
encoded ribonucleic acid particles (EBERs) by in situ
hybridization.
Diagnosis: Lymphomatoid granulomatosis
Clinical course
The patient was treated with a chemotherapy regimen of cyclophosphamide, doxorubicio, Oncovin and
prednisone (CHOP). Despite aggressive treatment,
progressive respiratory failure ensued and the patient
died˜ 1 week after the initiation of chemotherapy.
Discussion
Lymphomatoid granulomatosis (LYG) is a multisystem angiocentric lymphoproliferative disease with
a predilection for the lung, skin and nervous system.
LYG was originally classified among a benign group
of diseases characterized by pulmonary angiitis (perivascular inflammation) and granulomatosis (central
necrosis rather than granuloma formation), including
Wegener9s granulomatosis, Churg-Straus syndrome,
and bronchocentric granulomatosis [1]. Recent
advances have demonstrated that LYG is, in fact, a
B-cell lymphoma related to Epstein-Barr virus (EBV)
infection [2, 3]. New approaches to diagnosis and
therapy are being studied.
Diagnosis requires the presence of a triad of histological findings on biopsy specimens usually obtained
from the lung: a polymorphic lymphocytic infiltrate,
angiitis, and granulomatosis [1]. LYG is a destructive
lesion due to vessel occlusion by lymphoid infiltration
and subsequent necrosis. New molecular testing has
shown that LYG lesions consist of clonally-expanded
B-cells surrounded by a prominent polyclonal reactive
T-cell infiltrate [3]. Thus, LYG is now considered to
be a T-cell rich B-cell lymphoma.
A strong association exists between LYG and
infection with EBV [3, 4]. As in transplant and HIVassociated lymphoma, in most cases of LYG, EBV
RNA is present in the clonally-expanded B-cells.
The role of opportunistic pathogens in the development of LYG is further supported by the increased
occurrence of LYG in various forms of immune dysregulation. LYG has been reported in patients with
autoimmune diseases, HIV infection, transplantationassociated immunosuppression and primary immune
deficiencies such as Wiskott-Aldrich syndrome [5–7].
Furthermore, even LYG patients who are believed
to have normal immune systems have been found to
have subtle immunological abnormalities, such as a
decreased number of CD8 cells or defective delayedtype hypersensitivity responses. Thus, the pathogenesis of LYG appears to involve opportunistic
infection of a susceptible host.
LYG typically presents in the fifth and sixth
decades of life, with a slight male predominance.
Fever, cough, malaise and weight loss are common
symptoms and the most frequently affected organs are
the lung (90%), skin (40%), and nervous system (25%)
[4, 8]. Spleen and lymph nodes are rarely involved.
No laboratory finding are consistently found. Chestradiography findings include bilateral nodular lesions
(80–100%), which may rarely cavitate and predominantly involve the lower and peripheral lung fields.
Pleural effusions are present in one-third of patients.
The prognosis is quite poor with a median survival
of 14 months. The cause of death is usually from
respiratory failure or sepsis. Transformation into
high-grade lymphoma occurs in 13–49%. Less than
10% of cases resolve spontaneously [4, 8].
Previously, lymphomatoid granulomatosis was
treated with immunosuppressive medications, such
as glucocorticoids and cyclophosphomide. Recent
case series have used therapeutic approaches aimed
at improving rather than suppressing immune function. Moreover, suppressing viral replication may
be an effective alternative. For instance, two trials
of interferon-2a for the treatment of lymphomatoid
granulomatosis have demonstrated dramatic clinical
responses [9, 10]. Further studies using drugs that augment the immune system or suppress viral replication
are required.
COUGH, FEVER AND WEIGHT LOSS IN A YOUNG MALE
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